2 - foreign activators Flashcards
‘non-self’
substance that originates from outside the body at birth
generally bug e..g polymer (>3000 daltons)
examples of non-self molecules
microbes
allergens
foreign tissues
tyes of immune failure
non-responsiveness
over-responsiveness
examples of non-responsiveness of immune system
HIV
tumours
examples of over-responsiveness of immune system
sepsis
auto-immunity
features of innate immune system
fast
general
hours after exposure to infectious agent
features of adaptive immune system
specific
powerful
delayed - days after exposure
soluble receptors secreted from
cells
soluble receptors found in
blood
plasma
lymph
mucosal secretions
cell surface receptos found on
macrophages, neutrophils, lymphocytes and other somatic cells
properties of innate receptors
encoded in germline
pre-coded to recognise foreign activators
finite number - limited diversity
recognise structures common to different microbes
properties of adaptive receptors
take time to evolve
generated by gene recombination
massive diversity
recognise structures unique to different microbes
specific examples of immune system failure
spanish flu - 1918
TGN1412 - withdrawn 2006
spanish flu
1918-1920
most lethal flu outbreak ever recorded
20-40 million killed
20-30 year old heavily targeted (good immune systems)
over-activation of immune system led to increased production of cytokines
TGN1412
drug
a mono-clonal antibody to CD28 on T cells
passed animal testing
clinical trials - intended to only mildy activate immune system
caused cytokine storms and organ failure in humans
withdrawn from development in 2006
types of PAMPs
cell wall components
nucleic acid
conserved surface proteins
conserved stress proteins
examples of cell wall components - PAMPs
bacteria:
- peptidoglycan
- LPS
fungi:
- phospholipomannans
examples of nucleic acid -PAMPs
bacteria:
- CpG motif DNA
viruses:
- ssRNA
- Ds RNA
example of conserved surface proteins - PAMPs
bacteria:
- flagellin
examples of conserved stress proteins
bacteria:
- heat shock proteins
PPRs
soluble receptor examples
natural antibodies complement pentraxins collectins ficolins
PRRs
cell receptors examples
TLRs NOD-like receptors RIG-like receptors C-type lectin-like receptors scavenger receptors N-formyl met-leu-phe receptors
Toll-like receptors - structure
extracelllular domain - horseshoe structure, important for recognition
intracellular domain - dimerisation of 2 domains essential for signallign
examples of homodimer TLRs
TLR9 - recognises CpG DNA
TLR5 - recognises flagellin
example of heterodimer TLR
what does it recognise
TLR7/8 - recognises ssRNA
what happens if there are too many TLRs
increased cytokine production
increased production of TRanscription factors
inflammatory cascde
describe TLR4 binding and signalling
TLR4 allows macrophage to recognise LPS
LPS binding protein transports LPS to CD14
CD14 transports LPS to the TLR
LPS detected by MD-2
TLR dimerisation
signalling pathway initiated eg. NF-kappaB
LPS binding protein
accessory protein
transports LPS to CD14 receptor
CD14
cluster of differentiation gene receptor
either soluble
OR
binds to cell-surface via glycosylphatidylinositol anchor
transports LPS to TLR
MD-2
recognises LPS
forms complex with TLR4
what do antibodies recognise
recognise discrete epitopes on a protein antigen
antibdy recognition sites
at tips
can evolve and change to recognise different molecules
CDR
CDR
complementarity determining region
part of variable chain of an antibody
hyper-variable
determine specific binding of the antibody
epsilon toxin
important in disease in lambs and livestock
- all now vaccinated against
antibodies and gene recombinaton
lots of antibodies produced by different genes
each has different specificty
where does b cell production occur
progenitor cells in bone marrow
clonal deletion
the process by which self-recognising b cells are eliminated in the bone marrow
Product of clonal deletion
only B cells that recognise foreign antigens are allowed to mature and produce antibodies
